Therapeutic evaluation of Wumei Pill (WP) for nocturnal asthma in Bmal1 gene knockout mice.

Abstract

Objective: Previous clinical studies have demonstrated that Wumei Pill (WP), a traditional Chinese medicine formula, can effectively alleviate nocturnal asthma-related anxiety and improve nighttime symptoms. The therapeutic mechanism of WP may involve the regulation of inflammatory chemokines in peripheral blood. This mechanism is potentially linked to modulation of the circadian clock gene ARNT-like protein-1 (Bmal1), but precise pathways underlying this interaction remain unclear, requiring further investigation.

Methods: Bmal1 knockout and wild-type mice were utilized to establish asthma models. Techniques such as flow cytometry, RT-PCR, and ELISA were employed to measure the levels of serum inflammatory mediators, specifically IFN-γ, CXCL16, I-TAC, and PARC. Furthermore, the pathological alterations in airway thickness were assessed. Additionally, we investigated the regulation of the Bmal1 gene and its influence on the circadian rhythm-related recruitment of leukocytes, as well as the expression patterns of downstream mediators.

Results: Compared to the wild-type (WT) group, the model group showed significantly higher levels of CXCL16, I-TAC, and PARC (p < 0.05), as well as a notable decrease in IFN-γ expression. WP treatment effectively normalized the levels of these inflammatory factors in the model group, indicating a regulatory effect of WP on inflammatory chemokines.

Conclusion: The knockout of the Bmal1 gene, a crucial regulator of circadian rhythms, disrupts the circadian expression of inflammatory chemokines. Treatment with WP modulated Bmal1 expression, influencing the release of these mediators, offering a promising strategy for managing nocturnal asthma. Notably, wild-type nocturnal asthma mice exhibited significantly better control of airway inflammation compared to their Bmal1-deficient counterparts, highlighting the importance of circadian regulation in the pathophysiology of asthma.